Update: Skull base meningioma

Skull base meningioma

Epidemiology

As with intracranial meningiomas in other regions, skull base meningiomas demonstrate a femalepredominance, with a female-to-male ratio as high as 3:1.

Approximately 15% of meningiomas grow along the sphenoid ridge, with 10% developing in the posterior cranial fossa and 5% in the olfactory groove.

Meningiomas of the floor of the middle fossa are uncommon and tend to grow quite large before diagnosis.

Skull-base meningiomas are characterized by other recurrent mutations, including AKT1, SMOKLF4TRAF7 and POLR2A.

Classification

Treatment

Efforts to achieve a radical resection with dural margin are not suitable in many cases of skull base meningiomas, because of the neurovascular structures around the tumors.

Gamma knife radiosurgery (GKRS) is well established in the management of inaccessible, recurrent, or residual benign skull base meningiomas. Most series report clinical outcome parameters and complications in the short intermediate period after radiosurgery.

GKRS offers a highly durable rate of tumor control for World Health Organization grade 1 meningioma, with an acceptably low incidence of neurological deficits. The Karnofsky Performance Scale at the time of radiosurgery serves as a reliable long-term predictor of overall outcome 1).

Outcome

Peritumoral edema (PTE) in skull base meningiomas correlates to the absence of an arachnoid plane and difference in outcome.

A subset of benign (WHO grade I) skull base meningiomas show early progression/recurrence (P/R) in the first years after surgical resection.

Ko et al. retrospectively investigated the preoperative CT and MR imaging features for the prediction of P/R in skull base meningiomas, with emphasis on quantitative ADC values. Only patients had postoperative MRI follow-ups for more than 1 year (at least every 6 months) were included. From October 2006 to December 2015, total 73 patients diagnosed with benign (WHO grade I) skull base meningiomas were included (median follow-up time 41 months), and 17 (23.3%) patients had P/R (median time to P/R 28 months). Skull base meningiomas with spheno-orbital location, adjacent bone invasion, high DWI, and lower ADC value/ratio were significantly associated with P/R (P < 0.05). The cut-off points of ADC value and ADC ratio for prediction of P/R are 0.83 × 10- 3 mm2/s and 1.09 respectively, with excellent area under curve (AUC) values (0.86 and 0.91) (P < 0.05). In multivariate logistic regression, low ADC values (< 0.83 × 10- 3 mm2/s) and adjacent bone invasion are high-risk factors of P/R (P < 0.05), with odds ratios of 31.53 and 17.59 respectively. The preoperative CT and MRI features for prediction of P/R offered clinically vital information for the planning of treatment in skull base meningiomas 2).

Case series

2018

From a prospectively maintained database of 2022 meningioma patients who underwent Leksell stereotactic radiosurgery (SRS) during a 30-year interval, we found 98 patients with petroclival, 242 with cavernous sinus, and 55 patients with cerebellopontine angle meningiomas. Primary radiosurgery was performed in 245 patients. Patients included in this report had at least one CN deficit at the time of initial presentation and a minimum of 12 month follow up. Median age at the time of SRS was 58 years. Median follow up was 58 months (range 12-300 months), Median tumor volume treated with SRS was 5.9 cm3 (range 0.5-37.5 cm3), and median margin dose was 13 Gy (range 9-20Gy).

Tumor control was achieved in 229 patients (93.5%) at a median follow up of 58 months. Progression free survival rate (PFS) after SRS was 98.7% at 1 year, 96.4% at 3 years, 93.7% at 5 years, and 86.4% at 10 years Overall, 114 of the 245 patients (46.5%) reported improvement of CN function. Patients with CP angle meningiomas demonstrated lower rates of CN improvement compared to petroclival and cavernous sinus meningioma patients. Deterioration of CN function after SRS developed in 24 patients (10%). The rate of deterioration was 2.8% at 1 year, 5.2% at 3 years, and 8% at 10 years.

Primary SRS provides effective tumor control and favorable rate of improvement of preexisting CN deficit 3).

2011

Fourty-six patients harboring a skull base meningioma underwent an endoscope-assisted microsurgical resection. In 30 patients (65%), tumor parts which could not be visualized under the microscope were detected with the endoscope. In 26 patients (56%), these tumor remnants were removed under endoscopic view. Gross total resection was achieved in 35 patients (76%) and near-total resection in 11 (24%). There was no surgical mortality. The major complication was new cranial nerve deficit. The application of endoscopes was most useful in the small supraorbital craniotomies to look under the ipsilateral optic nerve and internal carotid artery as well as to visualize the diaphragm sellae and olfactory groove. In the retrosigmoid craniotomies, the endoscope was beneficial to inspect the internal auditory canal, to look into Meckel’s cave, or to inspect areas hidden behind the jugular tubercle and tentorial edge. There was no obvious complication related to the application of the endoscope. Endoscope assistance is particularly of value when skull base meningiomas are to be removed via small craniotomies to inspect blind corners which cannot be visualized in a straight line with the microscope. In addition, there is a benefit of using endoscopes with various angles of view in standard craniotomies and skull base approaches to look around bony and dural corners or to look behind neurovascular structures, by which the amount of skull base drilling and retraction to expose the tumor can be reduced 4).

1)

Cohen-Inbar O, Lee CC, Schlesinger D, Xu Z, Sheehan JP. Long-Term Results of Stereotactic Radiosurgery for Skull Base Meningiomas. Neurosurgery. 2016 Jul;79(1):58-68. doi: 10.1227/NEU.0000000000001045. PubMed PMID: 26421592.
2)

Ko CC, Lim SW, Chen TY, Chen JH, Li CF, Shiue YL. Prediction of progression in skull base meningiomas: additional benefits of apparent diffusion coefficient value. J Neurooncol. 2018 Jan 20. doi: 10.1007/s11060-018-2769-9. [Epub ahead of print] PubMed PMID: 29353434.
3)

Faramand A, Kano H, Niranjan A, Johnson SA, Hassib M, Park KJ, Arai Y, Flickinger JC, Lunsford LD. Cranial nerve outcomes after primary stereotactic radiosurgery for symptomatic skull base meningiomas. J Neurooncol. 2018 Apr 24. doi: 10.1007/s11060-018-2866-9. [Epub ahead of print] PubMed PMID: 29691775.
4)

Schroeder HW, Hickmann AK, Baldauf J. Endoscope-assisted microsurgical resection of skull base meningiomas. Neurosurg Rev. 2011 Oct;34(4):441-55. doi: 10.1007/s10143-011-0322-9. Epub 2011 May 26. PubMed PMID: 21614425.

Glioblastoma immunotherapy

Glioblastoma immunotherapy

The application of immunotherapy for glioblastoma currently finds itself therefore at a pivotal crossroads. Critical to mapping a path forward will be the systematic characterization of the immunobiology of glioblastoma tumors utilizing currently available, state of the art technologies. Therapeutic approaches aimed at driving effector immune cells into the glioblastoma microenvironment as well as overcoming immunosuppressive myeloid cells, physical factors, and cytokines, as well as limiting the potentially detrimental, iatrogenic impact of dexamethasone, will likely be required for the potential of anti-tumor immune responses to be realized for glioblastoma 1).

Patients with glioblastoma (GBM) exhibit a complex state of immunodeficiency involving multiple mechanisms of local, regional, and systemic immune suppression and tolerance. These pathways are now being identified and their relative contributions explored. Delineating how these pathways are interrelated is paramount to effectively implementing immunotherapy for GBM 2).


Progress in the development of these therapies for glioblastoma has been slow due to the lack of immunogenic antigen targets that are expressed uniformly and selectively by gliomas.

Trials have revealed promising trends in overall survival and progression free survival for patients with glioblastoma, and have paved the way for ongoing randomized controlled trials 3) 4)


Some clinical trials are reaching phase III. Significant progress has been made in unraveling the molecular and genetic heterogeneity of glioblastoma multiforme and its implications to disease prognosis. There is now consensus related to the critical need to incorporate tumor heterogeneity into the design of therapeutic approaches. Recent data also indicates that an efficacious treatment strategy will need to be combinatorial and personalized to the tumor genetic signature 5).


A recurrent theme of this work is that immunotherapy is not a one-size-fits-all solution. Rather, dynamic, tumor-specific interactions within the tumor microenvironment continually shape the immunologic balance between tumor elimination and escape. High-grade gliomas are a particularly fascinating example. These aggressive, universally fatal tumors are highly resistant to radiation and chemotherapy and inevitably recur after surgical resection. Located in the immune-privileged central nervous system, high-grade gliomas also employ an array of defenses that serve as direct impediments to immune attack. Despite these challenges, vaccines have shown activity against high-grade gliomas and anecdotal, preclinical, and early clinical data bolster the notion that durable remission is possible with immunotherapy. Realizing this potential, however, will require an approach tailored to the unique aspects of glioma biology 6).


Clinical experiences with active specific immunotherapy demonstrate feasibility, safety and most importantly, but incompletely understood, prolonged long-term survival in a fraction of the patients. In relapsed patients, Van Gool et al developed an immunotherapy schedule and categorized patients into clinically defined risk profiles. He learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients. The developmental program allows further improvements related to newest scientific insights. Finally, he developed a mode of care within academic centers to organize cell therapy for experimental clinical trials in a large number of patients 7).


Current clinical trials take a multifaceted approach with the intention of harnessing the intrinsic cytotoxic capabilities of the immune system to directly target glioblastoma cancer stem cells (gCSC) or indirectly disrupt their stromal microenvironment. Monoclonal antibodies (mAbs), dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) T cell therapies have emerged as the most common approaches, with particular iterations incorporating cancer stem cell antigenic markers in their treatment designs. Ongoing work to determine the comprehensive antigenic profile of the gCSC in conjunction with efforts to counter the immunosuppressive tumor microenvironment holds much promise in future immunotherapeutic strategies against GBM. Given recent advancements in these fields, Esparza etal. believe there is tremendous potential to improve outcomes of GBM patients in the continuing evolution of immunotherapies targeted to cancer stem cell populations in GBM 8).


Immunostimulating oligodeoxynucleotides containing unmethylated cytosineguanosine motifs (CpG-ODN) have shown a promising efficacy in several cancer models when injected locally. A previous phase II study of CpG-ODN in patients with recurrent glioblastoma (GBM) has suggested some activity and has shown a limited toxicity. This multicentre single-blinded randomised phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with de novo glioblastomas.

Patients with a newly diagnosed glioblastoma underwent large surgical resection and CpG-ODN was randomly administrated locally around the surgical cavity. The patients were then treated according to standard of care (SOC) with radiotherapy and temozolomide. The primary objective was 2-year survival. Secondary outcomes were progression free survival (PFS), and tolerance.

Eighty-one (81) patients were randomly assigned to receive CpG-ODN plus SOC (39 patients) or SOC (42 patients). The 2-year overall survival was 31% (19%; 49%) in the CpG-ODN arm and 26% (16%; 44%) in the SOC arm. The median PFS was 9 months in the CpG-ODN arm and 8.5 months in the SOC arm. The incidence of adverse events was similar in both arms; although fever and post-operative haematoma were more frequent in the CpG-ODN arm.

Local immunotherapy with CpG-ODN injected into the surgical cavity after tumour removal and followed by SOC, although well tolerated, does not improve survival of patients with newly diagnosed GBM 9).


Epidermal growth factor receptor 3 (EGFRvIII) is present in approximately one-third of glioblastoma (GBM) patients. It is never found in normal tissues; therefore, it represents a candidate target for glioblastoma immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to represent a target of glioma and is presented by MHC I/II complexes. Dendritic cells (DCs) have great potential to sensitize CD4+ T and CD8+ T cells to precisely target and eradicate GBM.

Li et al. show that PEPvIII could be loaded by DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to precisely kill U87-EGFRvIII cells. In addition to inhibiting proliferation and inducing the apoptosis of U87-EGFRvIII cells, miR-326 also reduced the expression of TGF-β1 in the tumour environment, resulting in improved efficacy of T cell activation and killing via suppressing the SMO/Gli2 axis, which at least partially reversed the immunosuppressive environment. Furthermore, combining the EGFRvIII-DC vaccine with miR-326 was more effective in killing U87-EGFRvIII cells compared with the administration of either one alone. This finding suggested that a DC-based vaccine combined with miR-326 may induce more powerful anti-tumour immunity against GBM cells that express a relevant antigen, which provides a promising approach for GBM immunotherapy 10).

1)

Reardon DA, Wucherpfennig K, Chiocca EA. Immunotherapy for glioblastoma: on the sidelines or in the game? Discov Med. 2017 Nov;24(133):201-208. PubMed PMID: 29278673.
2)

Jackson CM, Lim M. Immunotherapy for glioblastoma: playing chess, not checkers. Clin Cancer Res. 2018 Apr 24. pii: clincanres.0491.2018. doi: 10.1158/1078-0432.CCR-18-0491. [Epub ahead of print] PubMed PMID: 29691293.
3)

Thomas AA, Fisher JL, Ernstoff MS, Fadul CE. Vaccine-based immunotherapy for glioblastoma. CNS Oncol. 2013 Jul;2(4):331-49. doi: 10.2217/cns.13.29. PubMed PMID: 25054578.
4)

Agrawal NS, Miller R Jr, Lal R, Mahanti H, Dixon-Mah YN, DeCandio ML, Vandergrift WA 3rd, Varma AK, Patel SJ, Banik NL, Lindhorst SM, Giglio P, Das A. Current Studies of Immunotherapy on Glioblastoma. J Neurol Neurosurg. 2014 Apr 5;1(1). pii: 21000104. PubMed PMID: 25346943.
5)

Kamran N, Calinescu A, Candolfi M, Chandran M, Mineharu Y, Assad AS, Koschmann C, Nunez F, Lowenstein P, Castro M. Recent advances and future of immunotherapy for glioblastoma. Expert Opin Biol Ther. 2016 Jul 13. [Epub ahead of print] PubMed PMID: 27411023.
6)

Jackson CM, Lim M, Drake CG. Immunotherapy for Brain Cancer: Recent Progress and Future Promise. Clin Cancer Res. 2014 Apr 25. [Epub ahead of print] PubMed PMID: 24771646.
7)

Van Gool SW. Brain Tumor Immunotherapy: What have We Learned so Far? Front Oncol. 2015 Jun 17;5:98. eCollection 2015. Review. PubMed PMID: 26137448.
8)

Esparza R, Azad TD, Feroze AH, Mitra SS, Cheshier SH. Glioblastoma stem cells and stem cell-targeting immunotherapies. J Neurooncol. 2015 Feb 15. [Epub ahead of print] PubMed PMID: 25682090.
9)

Ursu R, Carpentier A, Metellus P, Lubrano V, Laigle-Donadey F, Capelle L, Guyotat J, Langlois O, Bauchet L, Desseaux K, Tibi A, Chinot O, Lambert J, Carpentier AF. Intracerebral injection of CpG oligonucleotide for patients with de novo glioblastoma-A phase II multicentric, randomised study. Eur J Cancer. 2017 Jan 28;73:30-37. doi: 10.1016/j.ejca.2016.12.003. [Epub ahead of print] PubMed PMID: 28142059.
10)

Li J, Wang F, Wang G, Sun Y, Cai J, Liu X, Zhang J, Lu X, Li Y, Chen M, Chen L, Jiang C. Combination epidermal growth factor receptor variant III peptide-pulsed dendritic cell vaccine with miR-326 results in enhanced killing on EGFRvIII-positive cells. Oncotarget. 2017 Feb 17. doi: 10.18632/oncotarget.15445. [Epub ahead of print] PubMed PMID: 28412740.

Papillary tumor of the pineal region

Papillary tumor of the pineal region

The WHO 2007 definition of Papillary tumor of the pineal region (PTPR) is as follows: – “A rare neuroepithelial tumor of the pineal region in adults, characterized by papillary architecture and epithelial cytology, immunopositivity for cytokeratin and ultra structural features suggesting ependymal differentiation.“ 1).

First described by Jouvet et al., in 2003 who reported six cases and called it “Papillary Tumor of Pineal region.” The tumor’s clinicopathological characteristics as described and illustrated in that series were very similar to the description of some entities reported by neuropathologists from different parts of the world. Many more independent case reports were published after Jouvet et al.’s initial report 2).


Various other names, like papillary pineocytoma, pineal parenchymal tumor, choroid plexus tumor, ependymoma and papillary meningioma have been given to these tumors in earlier reports 3).

They arise from specialized ependymocytes in the subcommissural organ, which is located in the pineal region. Characterized by papillary architecture and epithelial cytology, immunopositivity for cytokeratin and ependymal differentiation. It is considered grade II-III by the World Health Organization.

A review of the literature was performed to collect all the cases published with gross total resection and no complementary treatment. In conclusion, there is still much to be learned about the pathogenesisprognosis and management of this tumor. 4).

Epidemiology

Papillary tumor of pineal region (PTPR) arises exclusively in the pineal region and occurs most commonly in adults with slight preponderance in females.

Till 2008, about 64 cases of PTPR have been reported 5)

Clinical

The clinical behavior is often aggressive. Headache of short duration is the common presenting symptom. This occurs due to increased intracranial tension as a result of compression of the aqueduct.

Diagnosis

They may also have a cystic component. CT imaging shows their hypodense nature and enhancement with contrast. MRI demonstrates hypointensity in T1-weighted (T1W) sequence and hyperintensity in T2-weighted (T2W) sequence and enhance with contrast 6).

Treatment

Limited reports suggest surgical resection is the mainstay of treatment

The findings suggest that radiotherapy provides durable local control, particularly when administered in the adjuvant setting after GTR 7).

Case series

Little is known about the prognostic markers that might aid to identify patients at increased risk for recurrence. Therefore, the prognostic value of histopathologic and clinical features was examined in a series of 21 patients. Median age of the 12 male and 9 female patients was 35 years (range, 10 to 56 y). On histopathologic examination, all tumors were characterized by loose papillary structures and tumor cells forming broad perivascular pseudorosettes showing cytokeratin expression. In addition, tumors showed increased cellularity (n=4; 19%), nuclear pleomorphism (n=4; 19%), solid growth (n=11; 52%), necrosis (n=8; 38%), increased mitotic activity (≥3 mitoses per 10 high-power fields [n=10; 48%]), and increased proliferation (Ki67/MIB1 index ≥10% [n=8/20; 40%]). Gross total resection could be achieved in 13/21 patients (62%). Postoperatively, 13 patients received radiotherapy and 4 patients chemotherapy. Median recurrence-free survival was 66 months in 19 patients, for whom detailed follow-up information was available. Twelve patients (63%) experienced tumor progression. Three patients (16%) died of disease. Among the clinical and histopathologic features examined, only increased mitotic activity (52 [8 to 96] vs. 68 [66 to 70] mo [median [95% confidence interval]]) and proliferative activity (29 [0 to 64] vs. 67 [44 to 90] mo) were significantly associated with recurrence (P<0.05). Tumors of the 3 patients who had succumbed to disease showed increased mitotic and proliferative activity.

Increased mitotic and proliferative activities are associated with worse prognosis in papillary tumors of the pineal region 8).

Case reports

A 34-year-old male with headaches, blurred vision and normal examination. Radiological study showed a nodulocystic lesion in the pineal region compatible with pineocytoma. Surgery was performed using an infratentorial supracerebellar approach, finding a cystic tumor in the quadrigeminal cistern which was completely resected. Histopathology reported a papillary tumor of the pineal region. The patient made good progress without adjuvant therapy, and after 57 months of follow-up he remained asymptomatic and free of recurrence 9).

1)

Kleihues P, Cavenee WK. Pathology and Genetics of Tumours of Nervous System, No. 21. Geneva: World health Organization; 1979. World Health Organization Classification of Tumors. Lyon: IARC Press; 2000.
2)

Jouvet A, Fauchon F, Liberski P, Saint-Pierre G, Didier-Bazes M, Heitzmann A, Delisle MB, Biassette HA, Vincent S, Mikol J, Streichenberger N, Ahboucha S, Brisson C, Belin MF, Fèvre-Montange M. Papillary tumor of the pineal region. Am J Surg Pathol. 2003 Apr;27(4):505-12. PubMed PMID: 12657936.
3)

Roncaroli F, Scheithauer BW. Papillary tumor of the pineal region and spindle cell oncocytoma of the pituitary: new tumor entities in the 2007 WHO Classification. Brain Pathol. 2007 Jul;17(3):314-8. PubMed PMID: 17598824.
4) , 9)

Cañizares Méndez MA, Amosa Delgado M, Álvarez Salgado JA, Villaseñor Ledezma JJ, Capilla Cabezuelo E, Díaz Crespo F. Papillary tumor of the pineal region: Case report and review of the literature. Neurocirugia (Astur). 2018 Apr 21. pii: S1130-1473(18)30029-0. doi: 10.1016/j.neucir.2018.03.003. [Epub ahead of print] English, Spanish. PubMed PMID: 29691144.
5)

Fuller GN. The increasing diversity of Pineal and Sellar region tumors, Americal Association Of Neuropathologists USCAP Companion Society Inaugral Meeting Denver, CO. 2008
6)

Epari S, Bashyal R, Malick S, Gupta T, Moyadi A, Kane SV, Bal M, Jalali R. Papillary tumor of pineal region: report of three cases and review of literature. Neurol India. 2011 May-Jun;59(3):455-60. doi: 10.4103/0028-3886.82773. PubMed PMID: 21743183.
7)

Edson MA, Fuller GN, Allen PK, Levine NB, Ghia AJ, Mahajan A, Brown PD, DeMonte F, Li J. Outcomes After Surgery and Radiotherapy for Papillary Tumor of the Pineal Region. World Neurosurg. 2015 Mar 5. pii: S1878-8750(15)00184-9. doi: 10.1016/j.wneu.2015.02.031. [Epub ahead of print] PubMed PMID: 25749579.
8)

Heim S, Beschorner R, Mittelbronn M, Keyvani K, Riemenschneider MJ, Vajtai I, Hartmann C, Acker T, Blümcke I, Paulus W, Hasselblatt M. Increased mitotic and proliferative activity are associated with worse prognosis in papillary tumors of the pineal region. Am J Surg Pathol. 2014 Jan;38(1):106-10. doi: 10.1097/PAS.0b013e31829e492d. PubMed PMID: 24121176.

Update: Intracranial chondroma

Intracranial chondroma

Intracranial chondroma are cysts of chondroid tissue, first reported by Hirschfeld in 1851 1)

Epidemiology

They are extremely rare and account for only 0.2% to 0.3% of all intracranial tumor2) 3).

They can be present at different regions within the cranial cavity especially the skull base 4)intrasellar 5),parasellar 6)intradural and especially falx 7).

Very occasionally observed in combination with intratumoral hemorrhage 8).

Despite a purported lack of any sex predilection there are reports of a slight female predominance 9).

Intracerebral location is extremely rare and has only been described in a few cases 10) 11) 12).

Etiology

Various theories have been proposed to determine the etiology of intracranial chondromas but none has succeeded to ascertain a definite cause of origin. The most commonly accepted explanation for skull base chondromas is embryonic remnants of chondrogenic cells along the base 13).

They grow slowly by expansion and mostly originate from rests of cartilaginous cells at sphenoethmoidal sutureand sphenooccipital suture 14).

The chondromas arising from the dura matter, choroid plexus, and cerebral cortex have been proposed to develop from metaplasia of meningeal fibroblasts and perivascular meninges 15). Similarly, proliferation of ectopic embryologic rests of cartilage cells, traumatic displacement of cartilage elements or inflammatory cartilaginous activation of fibroblasts have been suggested to be the cause of development of intracranial chondromas 16).

Clinical features

The presenting symptoms range from headaches to lower cranial nerve palsy. In some cases, proptosis, diplopia and varying degrees of visual activity impairment along with orbital extension have been reported. Patients often complain of forgetfulness and lack of concentration.

Generalized tonic–clonic seizures are also usually the presenting complaints in intracranial chondromas, which develop because of the gradual destruction of a large number of neurons that begin to fire at regular intervals. Focal neurological deficits may also result from mass effects of tumor.

Intracranial chondroma has also been reported as a component of Ollier’s multiple chondromatosis.

Pontine hemorrhage has also been associated with parasellar intracranial chondromas. Association of skull base chondromas has also been reported with Maffucci syndrome.

Intracranial chondromas may develop in a person at any age but they have been most frequently observed in the third decade.

Diagnosis

Bone destruction occurs in over 50% of the cases, whereas irregular calcifications are seen in about 60%. Intracranial chondromas may also produce hyperostosis of the inner table of the skull 17) 18) 19).

On X-ray, intracranial chondromas represent hyperostosis of the internal table of the skull 20). enhanced intracranial pressure and calcified portions21). Intradural convexity chondromas possess carved, tufted, ring-shaped calcified areas 22).

MRI has become an important diagnostic tool for intracranial chondromas. Brownlee et al. reported variable signal intensity at different levels of MRI in a case of intracranial chondroma. At T1 they reported less intensity whereas at T2 the signal appeared to be of middle to high intensity 23).

They are typically DWI hypointense with high apparent diffusion coefficient (ADC) values while meningiomas are typically DWI hyperintense with low ADC values 24).


A study reported that intradural chondromas possess two different CT appearances. The usually found type 1 shows mixed density with minimal or moderate enhancements. The rare type 2 shows an innermost less dense area containing a cyst 25).


Angiography shows displacement of vessels but no tumor stain 26) 27) 28).


Chondromas showed low uptake in PET images, which might be useful for differentiation between chondromas and chordomas 29).


In the past pneumoencephalography revealed displacement of basal cisterns and the ventricular system. A radionuclide brain scan may show abnormal uptake in the tumor 30).

Differential diagnosis

Preoperatively, chondromas can be difficult to distinguish from meningiomas. They may also be confused with chordomas, craniopharyngiomas or even arterial aneurysms 31) 32)

Tanohata et al. reported two instances of skull base chondromas that exhibited delayed contrast enhancement on CT after a high-dose of the contrast medium was administered. They suggested this CT feature to be employed in differential diagnosis of intracranial chondromas from meningiomas and neurinomas 33).

Treatment

In symptomatic patients, operative resection is sensible. In most cases total removal of the tumor is possible and leads to full recovery. When the finding is merely incidental in older patients, a watchful waiting approach is acceptable, given the benign and slow-growing nature of the lesion 34).

The current popular surgical approach for parasellar lesions is transcranial such as the orbitozygomatic approachsubtemporal approach. In surgical removal of skull base chondromas, it is advisable to try to confirm the diagnosis preoperatively with characteristic image findings and to consider the best approach in each case to decompress the involved nerves without any complications 35).

In cases of convexity chondroma, it is additionally recommended to remove the dural attachment 36) 37) 38).

Outcome

Usually postoperative observation reveals no recurrence of the lesion after complete resection. An adjuvant therapy is not necessary and the long-term prognosis is good 39) 40) 41).

The malignant form, chondrosarcoma, generally occurs later in life, presenting mostly in the fifth and sixth decades 42).

Case series

2011

Xin et al. retrospectively analyzed the clinical data of 30 patients (12 males and 18 females; mean age 35.4 years; age range 16-60 years) who had pathologically confirmed intracranial chondroma treated at our hospital from September 1996 to June 2008. Surgery was performed on all 30 patients: five patients underwent postoperative radiotherapy; 26 patients were followed up postoperatively for a mean duration of 45.8 months. The surgical approach was selected according to tumor location. Total resection was achieved in 11 patients, subtotal resection in 13, and partial resection in nine (three patients had recurrent chondroma). Follow-up showed that 21 patients recovered without recurrences, three had recurrence, and two patients died. The clinical manifestations included headache and multiple cranial nerve lesions. Imaging usually showed a well-demarcated extramedullary tumor, centrally located, without surrounding brain edema, partially calcified (73.3%) and with minimal vascularity, often accompanied by erosion and destruction of surrounding bone (56.7%). It is difficult to totally remove an intracranial chondroma, and it is not possible to differentiate a chondroma from a myxoma or chordoma at the cranial base on the basis of clinical manifestations and neuroradiological findings. Selection of the appropriate surgical approach is important for resection of the tumor 43).

1976

Four new cases are added to the previously recorded 122 cases 44).

Case reports

2018

A 25-year-old male patient with a giant convexity chondroma with meningeal attachment in the right frontal lobe that was detected after a first generalized seizure. Based on the putative diagnosis of meningioma, the tumor was completely resected via an osteoplastic parasagittal craniotomy. The postoperative MRI confirmed the complete tumor resection. Histopathological analysis revealed the presence of a chondroma 45).

2017

Giant convexity chondroma with dural involvement: Case report and review of literature 46).

2013

A 55-year-old female presented to the emergency room with a complaint of aphasia. Her initial brain computed tomography scan showed an intracranial hemorrhage in the left frontal area. After surgery, histopathological examination confirmed the diagnosis of a chondroma. Intradural chondroma is a rare, slow growing, benign intracranial neoplasm, but is even rarer in combination with an intratumoral hemorrhage. Chondromas are generally avascular cartilaginous lesions. This case was thought to be caused by the rupture of abnormally weak vessels derived from the friable tumor. Intradural chondromas may be included in the differential diagnosis of intracranial tumors with acute hemorrhages. 47).

2012

A 23-year-old Asian man presenting with intracerebral chondroma of the left frontal lobe, which was eroding the dura matter. The intracranial chondroma was completely removed by surgery 48).

2011

A 45-year old female is presented with a solitary intracerebral chondroma located in the right frontal lobe with no meningeal attachment 49).


An intracranial chondroma with intratumoral and subarachnoidal hemorrhage 50).

2007

Higashida et al. reported two cases of intracranial skull base chondroma and discussed the differential diagnosis and the treatment strategies. The first case was a 39-year-old male who presented with left exophtalmos, visual loss and oculomotor disturbance. MRI showed a huge tumor occupying the bilateral cavernous sinus. Partial removal of the tumor was performed through the left orbitozygomatic subtemporal approach. The second case was a 54-year-old male who presented with left hemiparesis. MRI showed a brain stem infarction with a huge tumor located at the right middle fossa. Partial removal was performed through the right orbitozygomatic subtemporal approach. In these two cases, the histopathological diagnosis of the tumors was benign chondroma and the size of residual tumors have not changed for one year without any additional therapy 51).


A Osteochondroma of the skull base 52).

2003

A rare case of a chondroma arising from the convexity dura mater 53).

2001

A case of intracranial giant chondroma originating from the dura mater of the convexity 54).

2000

Intradural convexity chondroma: a case report and review of diagnostic features 55).

1993

A rare case of chondroma originated from the dura mater of the cerebral convexity in a 16-year-old girl. Radiologic findings are reported with emphasis on computed tomography and magnetic resonance imaging scans, and histogenesis is briefly discussed 56).

1991

A rare case of Maffucci’s syndrome associated with enchondroma at the skull base, left internal carotid artery aneurysm, and goiter is reported. Two other previously reported cases of Maffucci’s syndrome with associated aneurysms and the present case suggest that Maffucci’s syndrome may be associated with aneurysm 57).


A 8-year-old female with Ollier’s disease (multiple enchondromatosis) developed an intracranial chondroma arising from the clivus, which was diagnosed by both computed tomography and magnetic resonance imaging 58).

1990

A rare case of parasellar chondroma accompanied by pontine hemorrhage is described. A review is made of the previously reported 6 cases of intracranial chondromas complicated with hemorrhage. A 21 year-old woman was admitted because of consciousness deterioration progressing to coma within a day, and right hemiparesis. CT scan showed a contrast-enhanced mass in the parasellar region and a hematoma in the brain-stem, which was clearly demonstrated by MRI to be abutted on the dorsal part of the tumor mass. The tumor was removed through frontotemporal craniotomy and confirmed histologically as chondroma. Postoperatively, the patient gradually regained consciousness and is hospitalized to rehabilitate hemiparesis 59).

1989

A case is presented in which a solitary chondroma arose from the clivus of a patient with Ollier’s disease 60).

1983

Intradural chondroma: a case report and review of the literature 61).

1981

A case of a huge intracranial frontoparietal osteochondroma in a 20-year-old man is reported. The presenting symptoms were headache, vomiting, and blurred vision. Apart from papilledema, no other abnormal neurological signs were present. A specific preoperative diagnosis could not be reached from the information provided by plain skull films, angiography, and radionuclide scan. The findings on computed tomography were those of a high density mass interspersed with small foci of lower densities, producing a honeycomb appearance, and surrounded by deposits of nodular calcification. The postcontrast scan showed a moderate degree of enhancement with preservation of the precontrast honeycomb pattern. These particular features may enable a correct preoperative histological diagnosis to be offered with a high degree of probability 62).

1969

Osteochondroma of the base of the skull causing an isolated oculomotor nerve paralysis. Case report emphasizing microsurgical techniques 63).

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Encephaloclastic cyst

Poorly circumscribed areas of parenchymal destruction associated with cystic components.

Encephaloclastic cysts provoked by intraventricular chemotherapy are very uncommon.

Rare complication of a malfunctioning methotrexate Ommaya reservoir 1) 2).

Pathogenesis

The pathogenesis may result from alterations in CSF pulsations with retrograde flow of intraventricular chemotherapy into the brain parenchyma and subsequent development of a local chemical encephalopathy.

Mella et al. report two rare cases of encephaloclastic cyst with intraventricular topotecan use. The patients were diagnosed and treated at The University of Texas MD Anderson Cancer Center. They consented to the publication of their laboratory results and imaging studies for educational purposes.

The patients presented with metastatic cancers (breast/lung) complicated by leptomeningeal disease. Ommaya reservoirs were placed in both cases and patients were initiated on intraventricular topotecan at 0.4 mg twice weekly. After approximately 12 intraventricular treatments, both patients developed confusion, seizures and headaches. MRI of the brain demonstrated cystic dilatation of the brain parenchyma around the catheter that connects to the reservoir dome and delivers the drug to the intraventricular space. The catheter was surrounded by vasogenic edema. Catheters were removed and analyzed and were found to be intact. CSF analyses showed no evidence of infection or malignancy. Intraventricular topotecan was discontinued and both patients demonstrated sustained clinical and radiological responses.

These cases highlight an atypical complication of intraventricular use of topotecan with successful management 3).

1)

Chowdhary S, Chalmers LM, Chamberlain PA. Methotrexate-induced encephaloclastic cyst: a complication of intraventricular chemotherapy. Neurology. 2006 Jul 25;67(2):319. PubMed PMID: 16864827.
2)

Lubomski M, Pell M, Lochhead A, Jude M. Encephaloclastic cyst: a rare complication of a malfunctioning methotrexate Ommaya reservoir. Intern Med J. 2018 Feb;48(2):224-226. doi: 10.1111/imj.13704. PubMed PMID: 29415363.
3)

Mella DB, Kamiya-Matsuoka C, Liao B, Tummala S, de Groot J. Recurrent encephaloclastic cyst induced by intraventricular topotecan. J Neurol Sci. 2015 Feb 15;349(1-2):52-3. doi: 10.1016/j.jns.2014.12.024. Epub 2014 Dec 24. PubMed PMID: 25598491.

Update: Cerebellopontine angle pilocytic astrocytoma

Cerebellopontine angle pilocytic astrocytoma

A rare case of a 55-yr old patient of pilocytic astrocytoma of the cerebellopontine angle mimicking a vestibular schwannoma. The tumor protruded into the porus acusticus causing enlargement of the internal auditory meatus, which is quite an unusual feature of glial tumor 1).


Schneider et al. report a pilocytic astrocytoma of the cerebellopontine angle in a child presenting with auditory neuropathy spectrum disorder 2).


Mirone et al. describe a rare case of pediatric pilocytic astrocytoma presented as a right cerebellopontine angle (CPA) mass, completely separated from the brainstem and arising from the proximal VIII cranial nerve portion.

A 12-year-old boy, with no evidence of neurofibromatosis type 2, presented with progressive hearing loss at the right ear and headache. An initial enhanced magnetic resonance examination suggested the diagnosis of schwannoma. The tumor was resected by a suboccipital retrosigmoid approach.

The case seems to be the first report of a primary pediatric CPA pylocitic astrocytoma arising from the VIII nerve complex and presenting internal auditory canal enlargement. It represents the third reported case of a primary CPA pilocytic astrocytoma (the second pediatric case with the first arising from V nerve) and the eighth report of primary CPA glioma, overall 3).


A case of pilocytic astrocytoma of the cerebellum mimicking an acoustic schwannoma. The tumour protruded into the porus acusticus and enlarged the internal auditory meatus, which is a quite unusual characteristic of glial tumours 4).

1)

Dutta G, Singh D, Singh H, Sachdeva D, Kumar V, Chaturvedi A. Pilocytic astrocytoma of the cerebellopontine angle mimicking vestibular schwannoma: report of a rare entity. Br J Neurosurg. 2017 Dec 26:1-3. doi: 10.1080/02688697.2017.1419163. [Epub ahead of print] PubMed PMID: 29278012.
2)

Schneider F, Kompis M, Ozdoba C, Beck J, Caversaccio M, Senn P. Pilocytic astrocytoma of the cerebellopontine angle in a child presenting with auditory neuropathy spectrum disorder. Otol Neurotol. 2015 Apr;36(4):e101-3. doi: 10.1097/MAO.0000000000000355. PubMed PMID: 24781101.
3)

Mirone G, Schiabello L, Chibbaro S, Bouazza S, George B. Pediatric primary pilocytic astrocytoma of the cerebellopontine angle: a case report. Childs Nerv Syst. 2009 Feb;25(2):247-51. doi: 10.1007/s00381-008-0690-9. Epub 2008 Aug 9. PubMed PMID: 18690462.
4)

Takada Y, Ohno K, Tamaki M, Hirakawa K. Cerebellopontine angle pilocytic astrocytoma mimicking acoustic schwannoma. Neuroradiology. 1999 Dec;41(12):949-50. PubMed PMID: 10639675.